Automated cascade impactor

ABSTRACT

An automated cascade impactor comprises an extension mechanism operable to couple to a plurality of impactor stages. The extension mechanism is operable to compress and separate impactor stages of the plurality of impactor stages via automation. The system provides a plurality of isolation stages operable to be automatically inserted between respective impactor stages when the impactor stages are separated by the extension mechanism. The system provides the plurality of isolation stages to be automatically compressed between impactor stages to isolate each impactor stage from at least one adjacent impactor stage. The plurality of isolation stages is operable to be automatically uncompressed and removed from between the impactor stages. The isolation stages allow automated extraction of particulate matter, cleaning and drying of interior surfaces of each impactor stage.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to International ApplicationPCT/US2007/08924 filed on Apr. 10, 2007 which claims priority toProvisional Application 60/744,663 filed on Apr. 11, 2006, entitled,“AUTOMATED CASCADE IMPACTOR”, the contents and teachings of which arehereby incorporated by reference in their entirety.

FIELD OF INVENTION

Embodiments disclosed herein relate to the field of measurement ofparticle sizes in fluids. Example embodiments include devices andmethods for measurement of particle sizes in an air sample, wherever thesample is derived. More specifically embodiments disclosed herein arerelated to measurement of particle sizes from dose samples of inhalationdevices.

BACKGROUND OF THE INVENTION

A conventional Cascade Impactor is a device used to determine theaerodynamic particle size distribution and mass concentration levels ofsolid particulates and liquid aerosols, from aerosolized dry powder andaerosolized liquid drug samples injected into the Cascade Impactor.Cascade Impactors are also used by the environment control andmonitoring industry to determine particulate distributions from airsamples. A variety of cascade impactors are commercially available. Onereason for using Cascade Impactors in a testing environment is that airflowing inside the Cascade Impactors simulates air flowing into a humanlung.

When delivering drugs through the respiratory tract to the lungs,whether in the form of micro ionized powders, or in the form of micronsized droplets of aerosolized mist from a solution, it is important toknow the particle size distribution of the drug. Only drug particles ofsizes generally less then 5 microns in diameter can penetrate deep intothe lungs, and into the bronchi. Bigger particle sizes get ingested, andexcreted out of the human body. The deep lung provides an enormousamount of surface area for the active drug substance to get absorbed inthe blood steam, and thus permits the efficacious use of lower doses ofdrugs to get the same or better physiological response than drugdelivery through the oral drug delivery route. Measurement of particlesize distribution from injection of the drug into the Cascade Impactorsis called a Dose Determination. The Dose Determination data from theCascade Impactors is an integral part of a submission to the FDA as partof the NDA. Thousands of Dose Determinations need to be done, in orderto meet the FDA's submission criteria for a new inhalation drug.Following the drug approval, thousands of Cascade Impactors tests arestill needed to be performed over the lifetime of the inhalation drug,as an on-going quality control measure to continually prove to the FDAthat the performance of the inhalation drug continues to meet theapproval criteria of the drug.

Thus, in order to judge how efficacious the inhalation drug is whenusing inhalation devices, it becomes vitally important to generate theparticle size distribution of doses of drugs delivered, and to fine tunethe formulation of the inhalation drug.

Of the variety of Cascade Impactors commercially available, theconventional Andersen Cascade Impactor is the most popular. However,obtaining a Dose Determination from the Andersen Cascade Impactor it isvery labor intensive, and therefore, an expensive process. Each DoseDetermination from a contract lab can cost upwards of $1000. Typicalthroughput from each analyst operating an impactor to obtain a dosedetermination is two Dose Determinations per day. In addition, there aremany parts that need to be carefully disassembled, and washed during useof a conventional cascade impactor to obtain a Dose Determination.Samples must be manually and very carefully collected from some of theimpactor parts, and those parts must then be manually assembled again inpreparation of the next Dose Determination. Therefore, manuallydetermining a Dose Determination from the Andersen Cascade Impactor isvery error prone and time consuming.

Conventional Andersen Cascade Impactors on the market today arefabricated using either Aluminum or Stainless Steel. A conventionalAndersen Cascade Impactor is made up of a variable number ofclassification or impactor stages consisting of a series of jets andImpaction Plates. The number of Impactor Stages and Impaction Platesused to make up a column of the Andersen Cascade Impactor are variable,and depend on the drug and the particle size ranges that are to bemeasured. The Impaction Stages are stacked on top of each other, withsucceeding Impaction Stages having smaller orifice diameters. Below eachImpactor Stage is an Impaction Plate. During operation, as the drugsuspended in an aerosol stream is delivered into the throat of theimpactor and into the set of impaction stages, at each Impaction Stage,the aerosol stream passes through the jets or orifices and impacts uponthe Impaction Plate.

Each Impactor Stage contains a multitude of orifices of the samediameter for that stage. Particles in the aerosol stream withsignificant inertia will settle upon the Impaction Plate for a givenstage, while smaller particles pass as aerosols on to the next jetImpactor Stage. By designing consecutive Impactor Stages with higheraerosol jet velocities, smaller diameter particles are collected at eachsubsequent Impactor Stage (e.g. upon the impactor plate for that stage)giving the cascade affect of separation. The bottommost or lowestImpactor Stage contains a filter, to collect any drug that has not beencollected on the Impaction Plates or the Impactor Stages. Typically thefilter utilized is made of fiber media, or a very fine stainless steelmesh.

Sandwiched between succeeding stages is an O-Ring, so that all of theairflow is through the Impactor Stages, and none of the airflow leaksout of a seal formed between each impactor stage. Preventing airflowfrom leaking out of the Impactor is very important for obtainingreproducible experimental results. The Impactor Stages in a conventionalimpactor are tightly held by spring-loaded clamps, spaced 120 degreesapart around the circumference of the impactor, to ensure uniformclosing pressure, and thus keeping the Impactor Stages tightly sealed.At the top of the stage assembly is a Pre-Separator Stage that simulatesthe back of the throat. The Pre-Separator Stage is where the bulk of thelarger particle sizes are collected. Above the Pre-Separator is aGlass-Entry Throat. The inhaler is fitted into the Glass Entry Throatusing an adapter.

The particle size range collected at each of the Impactor Stages dependson the jet orifice velocity of the specific Impactor Stage, the distancebetween the orifices and the collection surface, and the collectioncharacteristics of the preceding Impactor Stage.

The combination of a constant flow rate, and successively smallerdiameter orifices increase the velocity of sample air as it cascadesthrough the Andersen Cascade Impactor, resulting in the impaction ofprogressively smaller particles in the succeeding Impactor Stages.

To operate the conventional Andersen Cascade Impactor, vacuum is appliedto the bottommost Impactor Stage containing the filter, and a constantairflow is established through the Andersen Cascade Impactor. Theinhaler is attached to the Glass Entry Throat on top of thePre-Separator, and the drug is “inhaled” by the Impactor by dispensingone dose of the drug within the aerosol stream emitted from the inhalerinto the throat of the impactor via the mouthpiece adapter. As the drugparticles of differing particle size within the aerosol stream passthrough the impactor, the particles get deposited onto differentImpaction Plates, with the bigger particles on the top and smallerparticles on the bottom Impaction Plates. After dispensing a single doseof the drug into the impactor, the Impaction Plates and the ImpactorStages are then manually disassembled by hand and each one of themcarefully washed with solvent. Samples are collected in duplicate fromeach collection plate surface in the Andersen Cascade Impactor, and ananalyst in the testing lab manually applies an HPLC technique todetermine the drug content or collection amount of the surface for agiven stage. The inhaler is weighed before and after drug injection intothe Automated Andersen Cascade Impactor. Assuming mass balance, theparticle size is deduced from the layer it was collected and theparticle size distribution for the dose is drawn up.

Particle sizes less then 3-5 microns are the particles that travel deepinto the lungs, permitting ready absorption of the drug into the blood,and thus are most efficacious. For this reason the US FDA and otherregulatory agencies throughout the world require extensive particle sizedistribution data from the drug companies. At about two DoseDeterminations per day using a conventional cascade impactor thatoperates by performing the test manually, it can take years to generatethe data and get regulatory approval from the FDA.

SUMMARY OF THE INVENTION

Conventional technologies for obtaining particle size distribution datausing conventional cascade impactors suffer from a variety ofdeficiencies. In particular, obtaining particle size distribution usingconventional impactors provides very low throughput since conventionalimpactors rely on completely manual setup, operation, testing and dosedetermination. Additionally, the manual process is very prone to a greatdegree of operator induced variability in the data produced. Eachoperator (e.g. lab technician or analyst) washes the many components ofthe Andersen Cascade Impactor a little differently, thus causinginconsistency in the amount of drug collected from each stage and eachImpaction plate. This inconsistent human washing of the plurality ofimpactor surfaces further affects the recovery of a drug from the sameapparatus for subsequent Dose Determinations. This operator inducedvariability precipitates the need for additional Dose Determinationsthat cause delay in submission of data by the drug companies to the FDA,and thus also delay the approval of drugs by the FDA. Delays due tooperator induced variability, and low throughput due to manualoperations of the ACI can cause the loss of hundreds of millions ofdollars in lost revenue.

Embodiments disclosed herein significantly overcome such deficienciesand provide an Automated Cascade Impactor that allows multiple DoseDeterminations per day, and substantially eliminates the operatorinduced variability associated with subsequent Dose Determinations. Inparticular, the methods and apparatus describe herein provide a roboticautomated cascade impactor that provides automation of the process ofcoupling the impactor stages together during delivery of a sample dose,as well as automation of collection of the drug sample from eachimpactor stage and cleaning each impactor stage.

In an example embodiment, the Automated Cascade Impactor utilizes anExtension Mechanism operable to couple to a plurality of ImpactorStages. The Extension Mechanism is operable to compress and separateImpactor Stages with the Impaction Plates of the plurality of ImpactorStages via automation. When just the impactor stages are compressed inan automated manner, the drug dose can be delivered into the impactor.Thereafter, the automated cascade impactor can automatically uncompresseach impactor stage, leaving a space between each impactor stage. Theplurality of Isolation Stages is operable to be automatically insertedbetween respective Impactor Stages when the Impactor Stages areseparated by the Extension Mechanism. The plurality of Isolation Stagesare then automatically compressed between Impactor Stages with theImpaction Plates to isolate each Impactor Stage from at least oneadjacent Impactor Stage. The plurality of Isolation Stages is operableto be automatically uncompressed and removed from between the ImpactorStages.

In example embodiment disclosed herein, the Automated Cascade Impactorutilizes an extension mechanism that has impactor mounts that hold eachimpactor stage, and that move along an extension guide, ensuring truevertical motion.

In example embodiment disclosed herein, the Automated Cascade Impactorutilizes an extension actuator that collectively compresses IsolationStages and Impactor Mounts (and hence the impactor stages), in asynchronized and symmetric manner, by means of being attached tosucceeding linkages and the collective Extension Assembly actuated by anExtension Actuator. Three Extension Actuator guides are used, eachspaced 120 degrees apart to provide uniform opening and closing of theAutomated Cascade Impactor assembly. In one example embodiment disclosedherein, the Automated Cascade Impactor ensures deposition of particulatematter within each Impactor Stage and on each Impaction Plate.

In one example embodiment disclosed herein, the Automated CascadeImpactor applies a compressive force to insure complete sealing ofImpactor stages with the Impaction Plate when injecting a drug throughthe Glass Entry port of a throat, and ensures sealing the ImpactorStages when the Isolation stages are inserted between impactor stages inthe sample collection mode.

In an example embodiment disclosed herein, the Automated AndersenCascade Impactor utilizes hydraulic, magnetic and/or electromechanicalforce to actuate the Extension Actuators and isolation actuator.

In an example embodiment disclosed herein, the Automated CascadeImpactor sandwiches the Isolation Stages between Impactor Stages withthe Impaction Plates.

In example embodiment disclosed herein, the Automated Cascade Impactorinjects and extracts fluids through Fluid Ducts in each Isolation Stage.

In example embodiment disclosed herein, the Automated Cascade Impactorutilizes an Oscillation Mechanism to agitate the Automated CascadeImpactor assembly in at least one of: a horizontal axis of rotation, avertical axis of rotation, and a conical axis of rotation.

In example embodiment disclosed herein, the Automated Cascade Impactorcomprises an entry throat that is exchangeable.

In an example embodiment disclosed herein, the Automated CascadeImpactor provides a mechanism that is easy and economical tomanufacture, and operate.

In an example embodiment disclosed herein, the Automated CascadeImpactor sandwiches, between Impactor Stages, an imaging system thattakes images of the orifices, so that the diameters of the orifices maybe accurately measured.

In example embodiment disclosed herein, the Automated Andersen Impactorautomates the determination of particle size distribution, using theAutomated Cascade Impactor into which samples are injected. In oneconfiguration, the impactor stages mounted within the impactor mountsare those of a conventional Andersen Cascade Impactor, thus producing anAutomated Andersen Cascade Impactor. In the Automated Andersen CascadeImpactor, the length of the Automated Cascade Impactor column (when theextension mechanism compresses only the impactor stages) remainsunaltered (as compared to a manual conventional impactor, such as anAndersen Cascade Impactor) for delivery of the sample into the AutomatedAndersen Cascade Impactor using an aerosolized inhalation device, or anyother device for that matter. Thus, the flight time and the path of theparticles inside the Automated Andersen Cascade Impactor remainunaltered. This negates the need to perform bridging studies (had theAndersen Column been altered) with respect to current data. For the samereason, comparison of particle size distribution with data associatedwith other studies remains the same (i.e., bridging studies are notrequired).

When preparing the samples (from the dose injected into the AutomatedCascade Impactor while only the impactor stages are compressed), theImpactor Stages are then extended or separated by means of an ExtensionMechanism(s), and the Extension Actuator as if they were bellows.Isolation Stages are then inserted and interleaved/sandwiched betweenthe extended Andersen Impactor Stages and Andersen Impactor ImpactionPlates (providing the interior surfaces upon which particular mattersamples collect in each impactor stage). Then, the entire assembly issymmetrically closed (as a bellow is closed) or symmetrically compressedwith the Extension Guides assuring true motion in the sense thatImpactor Stages and the Isolation Stages sandwiched between them remainparallel and in alignment with each other. This ensures leak-proofclosure when this assembly is closed and compressed.

Upon successful leak-proof closure, each impactor stage is completelyisolated from the others. Solvents are injected into each AutomatedImpactor isolation Stage through valves mounted in the Isolation Stages.The Column Assembly is agitated and rotated or vibrated for apre-determined time to dissolve the samples from each Andersen ImpactorStage and respective Impaction Plate. Using pumps, the samples areextracted through Fluid Ducts in the Isolation Stages and transferredinto closed vials for chemical analysis.

After the solvents (extraction agents) have been pumped out, wash orcleaning solvents or agents are pumped in through valves mounted in theAutomated Impactor Isolation Stages. The Automated Cascade Impactor isagitated as before, and the wash solvent is pumped out. This cycle isrepeated for a pre-determined time. The stages are then dried usingnitrogen as a drying agent, and the stages are uncompressed andextended. The interleaved isolation stages are pulled out and theAutomated Cascade Impactor Column is closed (i.e. only the impactorstages are re-compressed). The closure is detected by electronicallymeasuring the difference between the inlet and exit airflow through theAutomated Cascade Impactor Column. If the difference between theairflows is within specifications, the Automated Andersen CascadeImpactor is ready for the next sample injection, then cleaning anddrying. If the difference between the airflows is not withinspecifications, the software instructs the Extension Actuator toincrease the closing force in graduated increments. If closure is stillnot detected, the software warns an operator of a system malfunction.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a high level view of the Automated Cascade Impactoraccording to one embodiment disclosed herein.

FIG. 2 illustrates a high level view of the Automated Cascade Impactorwherein the impactor stages are compressed, according to one embodimentdisclosed herein.

FIG. 3 illustrates a high level view of the Automated Cascade Impactorwherein the impactor stages are uncompressed, according to oneembodiment disclosed herein.

FIG. 4 illustrates a high level view of the Automated Cascade Impactorwherein the extension mechanism couples each impactor stage, and allowseach impactor stage to be coupled with at least one adjacent impactorstage, according to one embodiment disclosed herein.

FIG. 5 illustrates a view of the Automated Cascade Impactor when allimpactor and isolation stages are aligned and in a compressed state.

FIG. 6 illustrates agitation of the Automated Cascade Impactor from aside or bottom using various agitation patterns such as vibration,shaking, rotation (vertical, horizontal, conical) and the like to assistin extraction of the particulate matter sample from the interiorsurfaces of each stage.

FIG. 7 is a flow chart of processing operations performed by anAutomated Cascade Impactor as disclosed herein.

FIG. 8 shows details of an extension linkage as disclosed herein.

FIG. 9 shows details of separation stages and extension linkages asdisclosed herein.

FIG. 10 shows details of separation stages as disclosed herein.

FIG. 11 shows a pneumatic cylinder and ball joint mechanism operating asan oscillation mechanism.

FIG. 12 shows a pneumatic cylinder operating as an oscillationmechanism.

FIG. 13 shows a push pin mechanism operating as an oscillationmechanism.

DETAILED DESCRIPTION

Embodiments disclosed herein provide an Automated Cascade Impactor thatallows multiple Dose Determinations per day in a manner that is muchfaster than manual operation of a conventional cascade impactor, andsubstantially eliminates the operator induced variability associatedwith the current and subsequent Dose Determinations.

FIG. 1 illustrates an example embodiment of the Automated CascadeImpactor 160 used to test Dose Determination via an entry throat 165that is coupled (as will be shown in successive figures) to an uppermostimpactor stage 130-1 during compression of the plurality of impactorstages 130-N. The entry throat 165 allows coupling of a delivery device,such as an inhaler (not shown), for dispensing of particulate mattersuch a drug particulates in an aerosol spray (through the entry throat165 into the plurality of compressed impactor stages 130-N). In oneexample embodiment, the entry throat 165 is exchangeable. The AutomatedCascade Impactor 160 further includes an extension mechanism 135 that iscoupled to a plurality of impactor stages 130-N. The extension mechanism135 is operable to compress and separate impactor stages 130-N, asrequired and as will be explained, via automation. Generally, theextension mechanism includes a linkage 145 that couples each impactorhousing 140 (that mounts an impactor stage 130), the extension guides150, and extension actuator 110. In particular, as will be shown anddescribed in more detail in FIG. 2, the extension mechanism 135 is ableto initially compress just the impactor stages 130-N to automaticallyconfigure the impactor stages 130-N in position with each other foradministration of a dose regimen (a dose regimen can be one to manydoses) of a drug from an inhaler device (not shown in figure) coupled tothe throat 165. After administration of the drug particles to eachcompressed impactor stage 130, the extension mechanism 135 canuncompress the impactor stages 130-N to a position as shown in FIGS. 1and 3 (i.e., providing a space between each impactor stage). Once theimpactor stages have collected the drug sample (FIG. 2) and have beenseparated as shown in FIGS. 1 and 3), a plurality of isolation stages120-N are operable (via suspension and alignment provided by anisolation armature 115) to be automatically inserted (via an operationof an isolation actuator 155) between respective impactor stages 130-Nwhen the impactor stages 130-N are separated by the extension mechanism135 (i.e., after the drug has been delivered to each stage for testing).This configuration is shown in FIG. 4. The plurality of isolation stages120-N are then automatically compressed between impactor stages 130-N toisolate each impactor stage 130-1 from at least one adjacent impactorstage 130-1 as shown in FIG. 5. The compression is symmetric and theisolation stages 120 are able to vertically travel upward (e.g. slide)upon the isolation armature 155 (upon a hardened steel shaft) as eachimpactor stage 130 comes into contact with an adjacent isolation stage120. In this fully compressed configuration, each impactor stage 130 isautomatically precisely aligned and isolated from adjacent impactorstages via the insertion and symmetric compression of the interveningisolation stages 120. That is, the isolation stages 120 becomesandwiched and aligned between the impactor stages 130 as shown in FIG.5. Isolation stages 120 may also be referred to herein as separationstages. In the fully compressed configuration as shown in FIG. 5, theplurality of isolation stages 120-N each include fluid ducts 125 (thatcan include valves) that are operable to control and direct injection ofcollection fluid into each impactor stage to collect the particulatematter (i.e. the drug sample) that has been deposited onto interiorsurfaces of each impactor stage 130-1. The fluid ducts 125 andassociated valves of each isolation stage 120 are also operable toinject cleaning and drying fluids into each isolated impactor stage 130to clean and dry surfaces of the impactor stage 130. Entry ports of eachfluid duct into the internal voids defined within each impaction stagecan be positioned at an angle to provide a turbulent or whirlpool effectas the fluid enters and fills the internal area. This turbulence of theliquid extraction agent (used to collect the particulate matter drugsample) due to a direction of entry can assist in removing the materialfrom internal surfaces such as an impactor plate within each impactionstages 130. Details of separation stage 120 flexible coupling 121 to theisolation armature 115 and access and placement of fluid ducts (andvalves) 125 are shown in FIG. 10 for the reader's reference. Theplurality of Flexible Couplings 121-N allows wiggle of the plurality ofIsolation Stages 120-N so as to automatically align the Plurality ofIsolation Stages 120-N when they are sandwiched and compressed betweenthe plurality of Impactor Stages 130-N with the adjacent Impactor Stages130-N above and below then, as described elsewhere in this document forsample preparation and cleaning, after the dose injection step.

In one configuration, as shown in detail in FIG. 9, each isolation stage120 has an isolation housing 196 having an upper sealing edge 198 and alower sealing edge (on the underside, not visible in FIG. 9). Theisolation housing 196 is sized proportionately to a diameter of animpactor stage 130 (that may include an impactor plate) of a cascadeimpactor (such as an Andersen cascade impactor stage) such that at leastone of the upper sealing edge 198 and lower sealing edge can becompressed to at least one sealing edge 132 of an adjacent impactorstage 130 to isolate an internal volume 136 of the adjacent impactorstage when the stages 120 and 130 are compressed against each other. Thefluid duct(s) 125 (of which there are two per isolation stage 120 in theexample shown in FIG. 9) passing through the isolation housing 196 allowfluid communication with the isolated internal volume 136 of theadjacent impactor stage 130 for particulate matter drug sampleextraction, cleaning and drying on interior surfaces of that impactorstage 130 (such interior surfaces include an impactor plate of thatimpactor stage).

FIG. 2 illustrates an example embodiment of the Automated AndersenCascade Impactor 160 when the extension mechanism 135 symmetricallycompresses just the impactor stages 130-N via automation. An entrythroat 165 is coupled to an uppermost impactor stage 130-1 duringcompression of the plurality of impactor stages 130-N. The extensionmechanism 135 includes a coupling to a plurality of impactor mounts140-N. Each impactor mount 140-1 is coupled to a respective impactorstage 130-1 of the plurality of impactor stages 130-N. The impactorstages 130 can be those of a conventional cascade impactor, such as anAndersen Cascade Impactor. The impactor stages 130 for purposes of thisdescription can refer to the impactor mounts 140 as well as the Andersencascade impactor stage or housing mounted therein. Each impactor mount140-1 includes a linkage 145 that couples that impactor mount 140-1 toat least one adjacent impactor mount 140-2, and allows the extensionmechanism 135 to compress and separate adjacent impactor stages 130-N inan automated manner as required during different phases of operation ofthe impactor 160. Refer to FIG. 8 for a detailed view of the linkage 145as it relates to impactor stages 130. The plurality of isolation stages120-N, each including fluid ducts 125, are coupled to an isolationarmature 115 that includes the isolation actuator 155 and are positionedoff the side while just the impactor stages 130 are compressed. Thus,FIG. 2 represents a phase of configuration of the impactor 160 duringwhich a dose of a drug may be delivered into the entry throat 165 fordeposition of drug particulate matter on that dose onto interiorsurfaces of each impactor stage 130 (including surfaces of an ImpactionPlate within that stage).

In an example embodiment, the extension mechanism 135 includes at leastone extension guide 150 upon which each impactor mount 140-1 travelsduring compression and separation of impactor stages 130-N. Theextension guides 150 causes the plurality of impactor mounts 140-N andrespectively coupled impactor stages 130-N to be vertically alignedduring compression and separation. In the illustrated design, there arethree extension guides 150 arranged in a triangular and symmetricconfiguration and each impactor mount 140 is able to slide up and downthe extension guides 150 under guidance from the extension mechanismlinkage 145 as the extension actuator 110 raises the lowermost impactorhousing or mount 140-N (that mounts the lowermost impactor stage 130).

In an example embodiment, the extension actuator 110 is coupled to theextension mechanism 135 and can symmetrically compress the impactorstages 130 alone (as shown in FIG. 2), and can symmetrically separatethe impactor stages 130 making room for insertion of the isolationstages 120 in between each impactor stage 130, and can then operate tosymmetrically compress (and uncompress) the collection of alternatingimpactor stages 130 and isolation stages 120. The extension actuator 110is thus operable to provide compressive force to the extension mechanism135. The compressive force collectively compresses the impactor mounts140-N of the extension mechanism 135 towards each other in a sandwichingeffect. The impactor mounts 140 maintain alignment with each other vialinkage mechanisms 145 (of which there are three spaced symmetricallyaround the perimeter of the impactor mounts 140) that can slide up anddown (under control of the extension actuator 110) upon the extensionguides 150. This causes automatic alignment as well as compression ofeach impactor stage 130-1 (mounted within each impactor mount 140) to anadjacent impactor stage 130-2 during operation of the Automated CascadeImpactor 160 for the purpose of sample preparation (i.e. drug dosedelivery) and collection.

In an example embodiment, the extension actuator 110 is operable toprovide the compressive force via the extension mechanism 135 to eachimpactor stage 130-1 to seal each impactor stage together in preparationfor dose delivery. In one configuration, the compressive force isapplied in an increasing manner until seals formed between boundaries ofeach impactor stage 130-1 (compressed against the next impactor stage130) are sufficient to maintain a predetermined gas pressure applied toan internal volume defined by internal areas of the collectivelycompressed impactor stages 130-N. In an example embodiment, theextension actuator 110 is pneumatically operated, or electricallyoperated or may be electro-mechanically or magnetically operated. Oncethe impactor stages 130 are compressed as shown in FIG. 2, a dose ofdrug may be delivered via the entry throat 165 while the predeterminedair flow pressure remains applied to an internal volume defined by thecollectively compressed impactor stages 130-N. This air flow may becaused by drawing suction from the lowermost impactor stage 130-N, thussimulating inhalation by a person's lung. As the drug is delivered,particulate matter settles or impacts onto interior surfaces of eachcompressed impactor stage 130 and onto Impaction Plates in those stages.After drug delivery is complete, the air flow is stopped and it is nowtime for the automated cascade impactor 160 to perform the phase ofsample preparation and sample collection. This entails separating eachimpactor stage 130 and inserting there-between a respective isolationstage 120 to automatically collect the drug sample from a given impactorstage 130, as well as clean and dry interior surfaces of that impactorstage 130 in preparation for delivery of the next drug sample. Thisprocess can be repeated many times faster than a conventional cascadeimpactor operated in a manual manner by a human. As an example, a humancan manually operate a conventional Andersen Cascade Impactor to performtwo dose deliveries (and extractions and cleanings) in a 7-8 hour periodof time, whereas the system disclosed herein can deliver, extract andclean the cascade impactor in approximately one hour.

FIG. 3 illustrates an example embodiment of the Automated CascadeImpactor 160 after drug delivery, but prior to insertion of theisolation stages 120. In this example embodiment, the extension actuator110 is operable to release compressive force applied to the extensionmechanism 135 to collectively separate and lower the impactor mounts140-N of the extension mechanism 135 down away from each other, causingseparation of each impactor stage 130-1 from an adjacent impactor stage130-2 after deposition of particulate matter (i.e. drug sample delivery)within each impactor stage 130-1.

Once the impactor stages 130 are fully uncompressed and separated, theplurality of isolation stages 120-N are operable to be automaticallyinserted between respective impactor stages 130-N (i.e. after theextension actuator 110 operates to separate the impactor mounts 140-Nand impactor stages 130 away from each other by lowering the lowermostimpactor stage 130-N). During lowering of the lowermost impactor stage130-N, the linkage mechanisms 145 coupling each impactor mount 140maintain alignment of each stage 130 and also control the verticalspacing and stop location or placement of each stage once the lowermoststage is fully lowered. Thus the separation of each impactor stage 130-1from an adjacent impactor stage 130-2 takes place after deposition ofparticulate matter within each impactor stage 130-1 and when fullyseparated, each impactor stage 130 is spaced apart from one anotherallowing enough room for insertion of the isolation stages 120.

As further shown in FIG. 3, a plurality of isolation stages 120-N,including fluid ducts 125-N, are coupled to an isolation armature 115that includes an isolation actuator 155. The isolation actuator 155 maybe, for example, a hydraulic, mechanical or electric piston or servothat provides horizontal movement of the isolation armature 115 uponwhich each isolation stage 120 is mounted. The isolation actuator 155and armature 115, and Flexible Coupling 121 thus provide concurrentinsertion and alignment of each isolation stage 120 (mounted on theisolation armature 115) with at least one respective impactor stage 130during automatic insertion of the isolation stages 120 between impactorstages 130.

FIG. 4 shows the set of isolation stages 120 that are inserted andaligned with the set of impactor stage 130 via operation of theisolation armature 115 and the isolation actuator 155. In thisconfiguration, the two sets of alternating isolation and impactor stages120/130 can be compressed together. Note that the isolation armature 115allows vertical travel of each isolation stage 120 upon the isolationarmature 115 during both upward symmetric compression and downwardsymmetric separation of respective isolation stages 120 with impactorstages 130. Upon insertion and alignment of the isolation stages 120between respective impactor stages 130, operation of the extensionmechanism 110 allows the isolation stages to freely travel between, andsymmetrically compress with, impactor stages via connection to theisolation armature to allow collective compression and alignment of theimpactor stages and isolation stages. The isolation armature 115includes isolation stage stops 116 that, during separation of respectiveisolation stages 120 with impactor stages 130, cause each isolationstage 120 to stop downward vertical travel at a predetermined locationor stop position relative to at least one adjacent impaction stage 130.Details of the isolation stage stops 116 can be seen in FIG. 10 as well.In the illustrated configurations then, the isolation stages 120 do notrequire a separate vertical drive system from the impactor stages 130,but rather, simply maintain vertical alignment and spacing from eachother via the isolation armature 115 and associated isolation stagestops 116. During compression, the isolation stages may travel and slidefreely upward on the isolation armature and the extension actuatorraises the lowermost impactor stage 130, thus picking up each isolationstage 120 as a lower impactor stage 130 comes into contact with theisolation stage 120 located above. During compression then, asandwiching effect occurs from the bottom up of alternating impactor andisolation stages 130, 120.

In the configuration shown in FIG. 4, the extension actuator 110operates to provide compressive force (via the extension mechanism 135)to the plurality of impactor stages 130-N and isolation stages 120-Ninserted between respective impactor stages 130-N. The symmetriccompressive force causes a sandwiching effect between alternating andaligned isolation and impactor stages that results in isolation of aninternal volume of each impactor stage 130-1 from at least one adjacentimpactor stage 130-2 to create separately isolated impactor stages130-N.

FIG. 5 shows the resultant configuration when the isolation stages 120have been inserted and compressed with impactor stages 130 usingcompressive force 195 applied by the extension actuator 110 to allstages 120, 130. This configuration ensures a leak-proof closure as theinterleaved or overlapping stages 120 and 130 are compressed. Theleak-proof closure is detected by electronically measuring thedifference between an inlet and exit airflow through the AutomatedCascade Impactor Column of compressed stages (e.g., air flowdifferential between the uppermost stage and lowermost stage withinspecified limits). If the difference between the airflows is withinspecifications, the Automated Andersen Cascade Impactor is ready forextraction of the sample, then cleaning and drying. If the differencebetween the airflows is not within specifications, software controllingoperation of the impactor 160 instructs the Extension Actuator 110 toincrease the closing force 195 in graduated increments. If closure isstill not detected, the software warns an operator of a systemmalfunction. Since the isolation stages 120 “float” on the isolationarmature 115, they are able to rise and fall with the movement of theimpactor stages being compressed of released up or down, and yet remainaligned.

In this compressed configuration as shown in FIG. 5, each isolationstage 120 is able to operate to extract the particulate matter drugsample delivered onto interior surfaces of a respective impactor stage130. To do so, each isolation stage 120 includes at least one fluid duct125-1 allowing fluid communication with the now-isolated internal volumeof a respective impactor stage 130-1. Though not shown in the figures,flexible tubes may be attached to the fluid ducts 125 to supply andremove such fluid. In one example embodiment, at least one fluid duct125-1 of each isolation stage 120 is operable to supply and extract afluid collection agent to the internal volume of a respective impactorstage 130-1. This enables suspension and extraction, within the fluidcollection agent, of the particulate matter (e.g. drug sample particlesdelivered via the sample dose when the impactor 160 was configured asshown in FIG. 2) disposed on internal surfaces of that isolated impactorstage 130-1. This drug collection process allows the automated cascadeimpactor 160 to accurately collect, remove and clean a drug sampleseparately from each impactor stage 130 without human involvement.

After drug collection is complete using the extraction agent fluid, atleast one fluid duct 125-1 of each isolation stage 120-1 is operable tosupply a fluid cleaning agent to the internal volume of a respectiveimpactor stage 130-1 to enable cleaning of that isolated impactor stage130-1. Additionally, at least one fluid duct 125-1 of each isolationstage 120 is operable to supply a fluid drying agent (a liquid or gas)to the internal volume of a respective impactor stage 130-1 to enabledrying of internal surfaces of that isolated impactor stage 130-1. Thefluid cleaning agents and drying agents may be liquids or gases of atype known to those skilled in the art.

FIG. 6 shows an example embodiment that includes an oscillationmechanism 190 is coupled to the Automated Cascade Impactor 160. Theoscillation mechanism 190 is a motor, servo or other motion inducingmechanism that provides movement 191, 192, 193 (e.g. rotation, shaking,vibration, etc.) of at least a portion or all of the Automated AndersenCascade Impactor 160 after at least one fluid duct 125-1 of eachisolation stage 120-1 is operated to provide either the fluidcollection, cleaning and/or drying agent. Note the oscillation mechanismmay be coupled to a side portion of the assembly 160 or may be coupledto a bottom portion as shown in FIG. 6. It will be appreciated thatcoupling the oscillation mechanism 190 to other areas of the automatedcascade impactor 160 would work as well to enable oscillation or shakingof the assembly 160 to assist in drug extraction and cleaning of thesystem. As noted above, the fluid duct 125-1 is operated to supply thefluid collection agent to the internal volume of a respective isolatedimpactor stage 130-1. As an example, before full extraction of the fluidcollection agent, the movement of the Automated Cascade Impactor 160from the oscillation mechanism causes agitation of the fluid collectionagent for displacement of the particulate matter disposed on internalsurfaces of each isolated impactor stage 130-1.

In an example embodiment, the oscillation mechanism 190 is operable torotate the isolated impactor stages 130-N about at least one of ahorizontal axis of rotation 192, a vertical axis of rotation 191, and/ora horizontal or vertical conical axis of rotation 193, or a random axisof rotation. It is to be understood that while the figures shows anoscillation mechanism 190 coupled to a side and/or base 198 of theassembly, other embodiments allow vibration of the entire impactor 160and in such cases, the oscillation mechanism 190 can be affixed to otherareas such as to a top portion, or to any suitable mounting point thatis structurally sound. In a configuration attached to the bottomportion, the agitation or shaking pattern can be conical or orbital suchthat the collective set of compressed impactor stages and separationstages can be oscillated in a conical or circular or orbital manner. Itis also to be understood that variations in oscillation speed and timingand motion can be utilized to best cause the particulate matter to beremoved from interior surfaces and suspended in a liquid agent used forextraction. After cleaning, the extension mechanism 110 can operate tolower the lowermost impactor stage 130, causing each isolation stage 120to begin sliding downward along the isolation armature 115. As notedabove, the isolation armature includes isolation stage stops 116 (shownin FIGS. 4 and 10, that, during separation of respective isolationstages with impactor stages, cause each isolation stage 130 to stopdownward vertical travel at a predetermined location relative to atleast one adjacent impaction stage. Once uncompressing of the impactorstages 130 and isolation stages 120 is complete, the isolation actuator155 can be operated to move the isolation armature 115 and attachedisolation stages 120 from between the impactor stages 120.

FIG. 7 shows method steps performed when operating an automated cascadeimpactor as described herein.

In step 200, the automated cascade impactor 160 automatically (andsymmetrically) compresses together a plurality of impactor stages 120 ofthe automated cascade impactor as shown in FIG. 2. During this process,the impactor 160 can measure a pressure of an internal volume definedwithin the compressed stages to determine when compression force issufficient to form an appropriate seal between the compressed stages 120and 130.

Next, in step 201, automated cascade impactor 160 receives particulatematter dispensed into the plurality of impactor stages 120 while theyare compressed.

In step 202, the automated cascade impactor 160 automatically separatesthe plurality of impactor stages 120 as shown in FIGS. 1 and 3.

In step 203, the automated cascade impactor 160 automatically inserts(and maintains alignment of) a plurality of isolation stages 120 betweenimpactor stages 130 as shown in FIG. 4.

In step 204, the automated cascade impactor 160 automatically andsymmetrically compresses (and maintains alignment of) the impactorstages 130 and inserted isolation stages 120 to isolate each impactorstage 130 from at least one adjacent impactor stage 130, as shown inFIG. 5.

In step 205, the automated cascade impactor 160 supplies a fluidcollection agent, via each isolation stage 120, to the internal volumeof a respective impactor stage 130 to enable dissolution, suspension andextraction, within the fluid collection agent, of the particulate matterdisposed on internal surfaces of that isolated impactor stage. During orafter presentation of the fluid collection agent via ducts 125 (andassociated valves) the oscillation mechanism 190 can be used to shakeand agitate the fluid collection agent to aid in removing particulatematter from all internal surfaces of the impactor stages upon which thematerial may have been deposited (including the impactor plates of eachimpactor stage). The amount or volume of fluid collection agent can be ameasured or pre-calculated amount. After the shaking, fluid samples ofdissolved drug are collected by operation of pumps through the fluidducts 125 (and associated valves) attached to each of the isolationstages 120.

In step 206, the automated cascade impactor 160 supplies and thereafterextracts a fluid cleaning agent (through ducts and associated valves125), via each isolation stage 120, into the internal volume of arespective impactor stage 130 to enable cleaning of that isolatedimpactor stage. The oscillation mechanism 190 can also be used aftersupplying the cleaning agent, but before extraction, to assist in thecleaning process by agitating the assembly to cause the cleaning agentto thoroughly clean interior surfaces. After agitation, the cleaningagent can be extracted via suction applied to the fluid ducts 125 (viavalve control).

In step 207, the automated cascade impactor 160 supplies a fluid dryingagent to the internal volume of a respective isolated impactor stage 130to enable drying of internal surfaces of that isolated impactor stage.The drying agent may be in a gas or liquid state applied via fluid ducts125 under high or low pressure.

As noted above, during steps 205, 206 and 207, the impactor 160 canoperate an oscillation mechanism 190 to provide movement of at least aportion of the automated cascade impactor, for example after supplyingthe fluid collection agent to the internal volume of a respectiveisolated impactor stage, and before full extraction of the fluidcollection agent. The movement of the impactor 160 from the oscillationmechanism 190 causes agitation of the fluid collection agent fordisplacement and extraction of the particulate matter disposed oninternal surfaces of each isolated impactor stage. In this manner,substantially complete extraction is obtained. Oscillation can be usedduring cleaning and drying cycles as well.

FIGS. 11, 12 and 13 show example variations of the oscillation mechanism190. In FIG. 11, the oscillation mechanism 190 is a pneumatic cylinderand ball joint mechanism. In FIG. 12 the oscillation mechanism 190 is apneumatic cylinder and in FIG. 13 the oscillation mechanism 190 is apush pin mechanism.

In step 208, the automated cascade impactor 160 uncompresses andseparates isolation stages 120 and impactor stages 130, and removes theisolation stages 120 from between impactor stages 130 thus returning theconfiguration to that shown in FIGS. 1 and 3.

Processing then repeats back to step 200 for a new drug dose sample tobe delivered to the impactor and tested. Due to the automation of thisentire process, sample doses can be collected at approximately onesample per hour as opposed to only two samples per day when performedmanually using a conventional cascade impactor.

While configurations of the system and method have been particularlyshown and described with references to configurations thereof, it willbe understood by those skilled in the art that various changes in formand details may be made therein without departing from the scope of theinvention. As an example, more of less impactor and separator stages130, 120 can be used as may be needed for particular sample testing.Accordingly, the present invention is not intended to be limited by theexample configurations provided above.

1. An automated cascade impactor comprising: an extension mechanismoperable to couple to a plurality of impactor stages, the extensionmechanism operable to vertically compress and separate impactor stagesof the plurality of impactor stages via automation; and a plurality ofisolation stages operable to be automatically inserted betweenrespective impactor stages when the impactor stages are separated by theextension mechanism, and to be automatically compressed between impactorstages to isolate each impactor stage from at least one adjacentimpactor stage, and operable to be automatically uncompressed andremoved from between the impactor stages.
 2. The automated cascadeimpactor of claim 1 wherein: the extension mechanism includes aplurality of impactor mounts, each impactor mount coupling to arespective impactor stage of the plurality of impactor stages, eachimpactor mount including a linkage that couples and aligns that impactormount to at least one adjacent impactor mount and allows the extensionmechanism to symmetrically compress and separate adjacent impactorstages in an automated manner while maintain.
 3. The automated cascadeimpactor of claim 2 wherein: the extension mechanism includes at leastone extension guide upon which each impactor mount travels duringcompression and separation of impactor stages, the extension guidescausing the plurality of impactor mounts and respectively coupledimpactor stages to be vertically aligned during symmetric compressionand separation.
 4. The automated cascade impactor of claim 2 comprising:an extension actuator coupled to the extension mechanism, the extensionactuator operable to provide compressive force to the extensionmechanism to collectively and symmetrically compress the impactor mountsof the extension mechanism towards each other causing compression ofeach impactor stage to an adjacent impactor stage during operation ofthe automated cascade impactor for deposition of particulate matterwithin each impactor stage.
 5. The automated cascade impactor of claim 4wherein: the extension actuator is operable to provide the compressiveforce via the extension mechanism to each impactor stage, thecompressive force applied in an increasing manner until seals formedbetween boundaries of each impactor stage are sufficient to maintain apredetermined gas pressure and fluid-flow applied to an internal volumedefined by the collectively compressed impactor stages.
 6. The automatedcascade impactor of claim 5 wherein the extension actuator is at leastone of: pneumatically operated; and electrically operated.
 7. Theautomated cascade impactor of claim 2 comprising: an extension actuatorcoupled to the extension mechanism, the extension actuator operable torelease compressive force applied to the extension mechanism tocollectively and symmetrically separate the impactor mounts of theextension mechanism away from each other causing separation, whilemaintaining alignment, of each impactor stage from an adjacent impactorstage after deposition of particulate matter within each impactor stage.8. The automated cascade impactor of claim 7 wherein: the plurality ofisolation stages are operable to be automatically inserted betweenrespective impactor stages after the extension actuator operates toseparate the impactor mounts of the extension mechanism away from eachother causing separation, while maintaining alignment, of each impactorstage from an adjacent impactor stage after deposition of particulatematter within each impactor stage.
 9. The automated cascade impactor ofclaim 8 wherein: the extension actuator is operable to providecompressive force via the extension mechanism to the plurality ofimpactor stages and isolation stages inserted between respectiveimpactor stages, the compressive force causing isolation of an internalvolume of each impactor stage from at least one adjacent impactor stageto create separately isolated impactor stages.
 10. The automated cascadeimpactor of claim 9 wherein: each isolation stage includes at least onefluid duct allowing fluid communication with the isolated internalvolume of a respective impactor stage.
 11. The automated cascadeimpactor of claim 10 wherein the at least one fluid duct of eachisolation stage is operable to supply and extract a fluid collectionagent to the internal volume of a respective impactor stage to enabledissolution, suspension and extraction, within the fluid collectionagent, of the particulate matter disposed on internal surfaces of thatisolated impactor stage.
 12. The automated cascade impactor of claim 10wherein the at least one fluid duct of each isolation stage is operableto supply a fluid cleaning agent to the internal volume of a respectiveimpactor stage to enable cleaning of that isolated impactor stage. 13.The automated cascade impactor of claim 10 wherein the at least onefluid duct of each isolation stage is operable to supply a fluid dryingagent to the internal volume of a respective impactor stage to enabledrying of internal surfaces of that isolated impactor stage.
 14. Theautomated cascade impactor of claim 11 comprising: an oscillationmechanism coupled to the automated cascade impactor, the oscillationmechanism providing movement of at least a portion of the automatedcascade impactor during a time period after the at least one fluid ductof each isolation stage is operated to supply the fluid collection agentto the internal volume of a respective isolated impactor stage andbefore full extraction of the fluid collection agent, the movement ofthe impactor from the oscillation mechanism causing agitation of thefluid collection agent for displacement of the particulate matterdisposed on internal surfaces of each isolated impactor stage forsuspension within the fluid collection agent.
 15. The automated cascadeimpactor of claim 14 wherein: the oscillation mechanism is operable tooscillate the isolated impactor stages using at least one of: i) ahorizontal axis of rotation; ii) a vertical axis of rotation; and iii) aconical axis of rotation; iv) a random oscillation pattern; and v) anoscillation pattern including vibration.
 16. The automated cascadeimpactor of claim 1 wherein: the plurality of isolation stages arecoupled to an isolation armature including an isolation actuator thatprovides concurrent insertion and alignment of each isolation stage withat least one respective impactor stage during automatic insertion of theisolation stages between impactor stages.
 17. The automated cascadeimpactor of claim 16 wherein the isolation armature allows verticaltravel and provides alignment of each isolation stage upon the isolationstage armature during compression and separation of respective isolationstages with impactor stages, the isolation armature including isolationstage stops that, during separation of respective isolation stages withimpactor stages, cause each isolation stage to stop downward verticaltravel at a predetermined location relative to at least one adjacentimpaction stage.
 18. The automated cacade impactor of claim 16 whereineach isolations stage includes a Flexible Coupling allowing wiggle ofthe plurality of Isolation Stages so as to automatically align thePlurality of Isolation Stages when they are sandwiched and compressedbetween the plurality of Impactor Stages with the adjacent ImpactorStages above and below them.
 19. The automated cascade impactor of claim17 wherein upon insertion and alignment of the isolation stages betweenrespective impactor stages, operation of the extension mechanism allowsthe isolation stages to freely travel between impactor stages viaconnection to the isolation armature to allow collective compression ofthe impactor stages and isolation stages.
 20. The automated cascadeimpactor of claim 1 comprising: an entry throat coupleable to anuppermost impactor stage during compression of the plurality of impactorstages, the entry throat allowing coupling of at least one deliverydevice for dispensing of particulate matter through the entry throatinto the plurality of compressed impactor stages.
 21. The automatedcascade impactor of claim 20 wherein the entry throat is exchangeable.22. An automated cascade impactor comprising: a plurality of impactorstages; an extension mechanism vertically coupling each impactor stagein the plurality of impactor stages, the extension mechanism allowingeach impactor stage to be coupled with at least one adjacent impactorstage for deposition of a first particulate sample into the automatedcascade impactor, and the extension mechanism allowing decoupling ofadjacent impactor stages after deposition of the first particulatesample into the automated cascade impactor; at least one isolation stageoperable to: i) be automatically inserted between and compressed to atleast one impactor stage of the plurality of impactor stages andoperable to collect the first particulate sample from the at least oneimpactor stage; ii) clean the at least one impactor stage; and iii) beuncompressed and removed from the at least one impactor stage to allowrepetition of dispensing of at least one additional particulate sampleinto the automated cascade impactor.
 23. A method for operating anautomated cascade impactor to collect particulate matter dispensed intothe automated cascade impactor, the method comprising: automaticallyvertically compressing together a plurality of impactor stages of theautomated cascade impactor; dispensing particulate matter into theplurality of impactor stages; automatically separating the plurality ofimpactor stages; automatically inserting a plurality of isolation stagesbetween impactor stages; automatically vertically compressing theimpactor stages and inserted isolation stages to isolate each impactorstage from at least one adjacent impactor stage; and supplying andextracting a fluid collection agent, via each isolation stage, to theinternal volume of a respective impactor stage to enable suspension andextraction, within the fluid collection agent, of the particulate matterdisposed on internal surfaces of that isolated impactor stage.
 24. Themethod of claim 23 wherein automatically vertically compressing togethera plurality of impactor stages of the automated cascade impactor, andautomatically vertically compressing the impactor stages and insertedisolation stages to isolate each impactor stage from at least oneadjacent impactor stage comprises: measuring a pressure and fluid flowof an internal volume defined within the vertically compressed stages todetermine when compression force is sufficient to form an appropriateseal between the compressed stages.
 25. The method of claim 23comprising: supplying and extracting a fluid cleaning agent, via eachisolation stage, to the internal volume of a respective impactor stageto enable cleaning of that isolated impactor stage.
 26. The method ofclaim 23 wherein supplying and extracting a fluid collection agentcomprises: operating an oscillation mechanism coupled to the automatedcascade impactor, the oscillation mechanism providing movement of atleast a portion of the automated cascade impactor, after supplying thefluid collection agent to the internal volume of a respective isolatedimpactor stage, and before full extraction of the fluid collectionagent, the movement of the impactor from the oscillation mechanismcausing agitation of the fluid collection agent for displacement andextraction of the particulate matter disposed on internal surfaces ofeach isolated impactor stage.
 27. The method of claim 23 comprising:supplying a fluid drying agent to the internal volume of a respectiveisolated impactor stage to enable drying of internal surfaces of thatisolated impactor stage.
 28. An isolation stage comprising: an isolationhousing having an upper sealing edge and a lower sealing edge, theisolation housing sized proportionately to a diameter of an impactorstage of a cascade impactor such that at least one of the upper sealingedge and lower sealing edge can be compressed to at least one sealingedge of an adjacent impactor stage to isolate an internal volume of theadjacent impactor stage; and at least one fluid duct passing through theisolation housing, the at least one fluid duct allowing fluidcommunication with the isolated internal volume of the adjacent impactorstage.